Genetic Variant ATP6V1G2-DDX39B:n.184-999T>C (chr6-31543147-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000376185.5(ATP6V1G2-DDX39B):n.184-999T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,142 control chromosomes in the GnomAD database, including 4,425 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4425 hom., cov: 32)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

ATP6V1G2-DDX39B
ENST00000376185.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64

Publications

47 publications found

Variant links:

Genes affected

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B links:

DDX39B-AS1 (HGNC:39771): (DDX39B antisense RNA 1)

DDX39B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATP6V1G2-DDX39B	NR_037853.1 link	n.473-999T>C	intron_variant	Intron 2 of 12
DDX39B-AS1	NR_133674.1 link	n.*9A>G	downstream_gene_variant
DDX39B-AS1	NR_133675.1 link	n.*9A>G	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2-DDX39B	ENST00000376185.5 link	n.184-999T>C		intron_variant	Intron 2 of 12	2		ENSP00000365356.1		F2Z307

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35083

AN:

152000

Hom.:

4426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0625

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.231

AC:

35124

AN:

152118

Hom.:

4425

Cov.:

AF XY:

0.228

AC XY:

16969

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.202

AC:

8364

AN:

41484

American (AMR)

AF:

0.325

AC:

4969

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1554

AN:

3466

East Asian (EAS)

AF:

0.183

AC:

948

AN:

5180

South Asian (SAS)

AF:

0.222

AC:

1071

AN:

4818

European-Finnish (FIN)

AF:

0.103

AC:

1094

AN:

10582

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16181

AN:

68002

Other (OTH)

AF:

0.271

AC:

571

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1348

2696

4044

5392

6740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.245

Hom.:

14571

Bravo

AF:

0.249

Asia WGS

AF:

0.199

AC:

691

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

(source)

DANN

Benign

0.73

PhyloP100

-1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over